Characteristics and Significance of Tertiary Lymphoid Structures Based on Molecular Subtypes in Endometrial Cancer.

The purpose of this study is to investigate the characteristics and significance of tertiary lymphoid structures (TLSs) in endometrial cancer (EC) based on molecular subtypes. A total of 220 patients with EC were retrospectively enrolled, including 20 with polymerase epsilon ultramutated (POLE-mut), 63 with mismatch repair deficient, 32 with p53 abnormal, and 105 with no specific molecular profile. The presence and maturity of TLSs were determined by immunohistochemical markers (CD3, CD20, CD21, and Bcl6).

Evaluating language models for mathematics through interactions.

There is much excitement about the opportunity to harness the power of large language models (LLMs) when building problem-solving assistants. However, the standard methodology of evaluating LLMs relies on static pairs of inputs and outputs; this is insufficient for making an informed decision about which LLMs are best to use in an interactive setting, and how that varies by setting. Static assessment therefore limits how we understand language model capabilities.

mTOR Inhibition Prolongs Survival and Has Beneficial Effects on Heart Function After Onset of Lamin A/C Gene Mutation Cardiomyopathy in Mice.

Background: Mutations in encoding nuclear envelope proteins lamin A/C cause dilated cardiomyopathy. Activation of the AKT/mTOR (RAC-α serine/threonine-protein kinase/mammalian target of rapamycin) pathway is implicated as a potential pathophysiologic mechanism. The aim of this study was to assess whether pharmacological inhibition of mTOR signaling has beneficial effects on heart function and prolongs survival in a mouse model of the disease, after onset of heart failure.

Design of hepadnavirus core protein-based chimeric virus-like particles carrying epitopes from respiratory syncytial virus.

Respiratory syncytial virus (RSV) is one of the most important pathogens causing respiratory tract infection in humans, especially in infants and the elderly. The identification and structural resolution of the potent neutralizing epitopes on RSV fusion (F) protein enable an "epitope-focused" vaccine design. However, the display of RSV F epitope II on the surface of the widely-used human hepatitis B virus core antigen (HBcAg) has failed to induce neutralizing antibody response in mice.

Duloxetine reduces opioid consumption and pain after total hip or knee arthroplasty: a meta-analysis of randomized controlled trials.

Purpose: There is no consensus in the current literature on the analgesic role of duloxetine after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Thus, we designed this meta-analysis to reveal the analgesic effectiveness and safety of duloxetine in TKA or THA.

Methods: As of October 2022, two authors (L.

BacPE: a versatile prime-editing platform in bacteria by inhibiting DNA exonucleases.

Prime editing allows precise installation of any single base substitution and small insertions and deletions without requiring homologous recombination or double-strand DNA breaks in eukaryotic cells. However, the applications in bacteria are hindered and the underlying mechanisms that impede efficient prime editing remain enigmatic. Here, we report the determination of vital cellular factors that affect prime editing in bacteria.

Breaking NGF-TrkA immunosuppression in melanoma sensitizes immunotherapy for durable memory T cell protection.

Melanoma cells, deriving from neuroectodermal melanocytes, may exploit the nervous system's immune privilege for growth. Here we show that nerve growth factor (NGF) has both melanoma cell intrinsic and extrinsic immunosuppressive functions. Autocrine NGF engages tropomyosin receptor kinase A (TrkA) on melanoma cells to desensitize interferon γ signaling, leading to T and natural killer cell exclusion.

A Standardized Botanical Composition Mitigated Acute Inflammatory Lung Injury and Reduced Mortality through Extracellular HMGB1 Reduction.

HMGB1 is a key late inflammatory mediator upregulated during air-pollution-induced oxidative stress. Extracellular HMGB1 accumulation in the airways and lungs plays a significant role in the pathogenesis of inflammatory lung injury. Decreasing extracellular HMBG1 levels may restore innate immune cell functions to protect the lungs from harmful injuries.

Healthy ageing has divergent effects on verbal and non-verbal semantic cognition.

Semantic cognition refers to the storage and appropriate use of knowledge acquired over the lifespan and underpins our everyday verbal and non-verbal behaviours. Successful semantic cognition requires representation of knowledge and control processes which ensure that currently relevant aspects of knowledge are retrieved and selected. Although these abilities have been widely studied in healthy young populations and semantically impaired patients, it is unclear how they change as a function of healthy ageing, especially for non-verbal semantic processing.

Phytochemical consumption and the risk of teratozoospermia: findings from a hospital-based case-control study in China.

Study Question: Are dietary phytochemicals associated with the risk of teratozoospermia?

Summary Answer: Dietary intake of carotene, including total carotene, α-carotene, β-carotene as well as retinol equivalent, and lutein + zeaxanthin, were inversely correlated with the risk of teratozoospermia.

What Is Known Already: Phytochemicals are natural plant derived bioactive compounds, which have been reported to be potentially associated with male reproductive health. To date, no study has investigated the association between phytochemical intake and the risk of teratozoospermia.

Spatial attention modulates multisensory integration: The dissociation between exogenous and endogenous orienting.

Previous studies have separately found that exogenous orienting decreases multisensory integration (MSI), while endogenous orienting enhances MSI. It is currently unclear, however, why the two orientations have opposite effects on MSI. In the current study, we investigated the interaction between spatial attention and MSI in two experiments based on the cue-target paradigm.

Does animacy affect visual statistical learning? Revisiting the effects of selective attention and animacy on visual statistical learning.

Animates receive preferential attentional processing over inanimates because, from an evolutionary perspective, animates are important to human survival. We investigated whether animacy affects visual statistical learning-the detection and extraction of regularities in visual information from our rich, dynamic, and complex environment. Participants completed a selective-attention task, in which regularities were embedded in two visual streams, an attended and an unattended visual stream.

Influence of different spatial representations on the SNARC effect for letters: Electrophysiological evidence.

Studies have previously demonstrated that different spatial representations may affect the spatial-numerical association of response codes (SNARC) effect for numbers; however, limited studies have assessed the SNARC effect for letters. In this study, event-related potentials (ERPs) were used to measure the influence of two spatial representation modes (ruler and clock) on the SNARC effect. The ruler produced a SNARC-like effect; i.

Grammatical encoding of double-object alternations in Zhuang: Evidence for the one-stage model.

Production research has yielded mixed findings regarding whether grammatical encoding specifies grammatical functions and linear word order simultaneously or separately, supporting either one-stage or two-stage models. Here, we focused on the double object (DO) and shifted double object (SDO) constructions in Zhuang, an ethnic minority language in China because they differ only in linear ordering of the two nouns whose grammatical functions are direct object and indirect object, assuming the roles of Theme and Recipient, respectively. Using two structural priming experiments, we found that both DO and SDO constructions induced within-structure priming effects, but they did not prime each other.

Guide RNA engineering enables efficient CRISPR editing with a miniature Syntrophomonas palmitatica Cas12f1 nuclease.

Gene therapy is limited by inefficient delivery of large clustered regularly interspaced short palindromic repeat (CRISPR) effectors, such as Cas9 and Cas12a nucleases. Cas12f nucleases are currently one of the most compact CRISPR genome editors. However, the available toolkit of efficient Cas12f editors is limited.

Individual differences in executive attention and inhibitory control are related to spatial memory biases in adults.

Executive attention is involved in working memory; however, the role of executive attention in the maintenance of information in spatial working memory is debated. This study examined whether inhibitory control was related to spatial working memory biases in adults in a simple spatial memory task where participants had to remember one location on an otherwise blank computer screen. On some trials, a distractor was presented during the maintenance period.

Design of a mutation-integrated trimeric RBD with broad protection against SARS-CoV-2.

The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen.

Cancer-cell-derived GABA promotes β-catenin-mediated tumour growth and immunosuppression.

Many cancers have an unusual dependence on glutamine. However, most previous studies have focused on the contribution of glutamine to metabolic building blocks and the energy supply. Here, we report that cancer cells with aberrant expression of glutamate decarboxylase 1 (GAD1) rewire glutamine metabolism for the synthesis of γ-aminobutyric acid (GABA)-a prominent neurotransmitter-in non-nervous tissues.

Shift work and health outcomes: an umbrella review of systematic reviews and meta-analyses of epidemiological studies.

Study Objectives: Shift work is commonly increasing, and some physiological changes occur as workers sleep less and their circadian rhythms are disrupted. This umbrella review not only summarizes the evidence but also evaluates the validity of the associations of shift work with different health outcomes.

Methods: We searched the MEDLINE, Web of Science, and Embase databases from their inception to April 25, 2020.

Drug Conjugates of Antagonistic R-Spondin 4 Mutant for Simultaneous Targeting of Leucine-Rich Repeat-Containing G Protein-Coupled Receptors 4/5/6 for Cancer Treatment.

LGR4-6 (leucine-rich repeat-containing G-protein-coupled receptors 4, 5, and 6) are three related receptors with an upregulated expression in gastrointestinal cancers to various extents, and LGR5 is enriched in cancer stem cells. Antibody-drug conjugates (ADCs) targeting LGR5 showed a robust antitumor effect in vivo but could not eradicate tumors due to plasticity of LGR5-positive cancer cells. As LGR5-negative cancer cells often express LGR4 or LGR6 or both, we reasoned that simultaneous targeting of all three LGRs may provide a more effective approach.

Define Mesenchymal Stem Cell from Its Fate: Biodisposition of Human Mesenchymal Stem Cells in Normal and Concanavalin A-Induced Liver Injury Mice.

The pharmaceutical industry and clinical trials have been revolutionized mesenchymal stem cell-based therapeutics. However, the pharmacokinetics of transplanted cells has been little characterized in their target tissues under healthy or disease condition. A quantitative polymerase chain reaction analytical method with matrix effect was developed to track the biodistribution of human mesenchymal stem cells in normal mice and those with Concanavalin A (Con A)-induced liver injury.

How the size of exogenous attentional cues alters visual performance: From response gain to contrast gain.

The normalisation model of attention (NMoA) predicts that the attention gain pattern is mediated by changes in the size of the attentional field and stimuli. However, existing studies have not measured gain patterns when the relative sizes of stimuli are changed. To investigate the NMoA, the present study manipulated the attentional field size, namely, the exogenous cue size.

Resident memory T cells in tumor-distant tissues fortify against metastasis formation.

As a critical machinery for rapid pathogen removal, resident memory T cells (Ts) are locally generated after the initial encounter. However, their development accompanying tumorigenesis remains elusive. Using a murine breast cancer model, we show that Ts develop in the tumor, the contralateral mammary mucosa, and the pre-metastatic lung.